Premature birth is the leading cause of perinatal mortality and morbidity worldwide. The Perinatology Research Branch has defined preterm labor as a syndrome and determined that at least 25% of all preterm births are born to women with sub-clinical intrauterine infection. Moreover, we have provided evidence that many premature neonates are critically ill before birth and proposed that the onset of premature labor has survival value in the context of intrauterine infection. The goal of this project is to understand the pathophysiology of premature labor and delivery and the focus of our research this year is to determine the role of pro-inflammatory cytokines, their receptors and matrix metalloproteinases in term and preterm labor. Our work resulted in the following findings:1) Neutrophil collagenase, an enzyme capable of degrading collagen and other components of extracellular matrix of the fetal membranes, is elevated in patients who have preterm premature rupture of membranes, intrauterine infection or premature labor. 2) Matrilysin, a matrix degrading enzyme implicated in the host defense against infection, is dramatically elevated in the amniotic fluid of patients with intrauterine infection but not in patients with labor or rupture of membranes. The enzyme may activate natural antimicrobial peptides (alpha defensins), which has been previously demonstrated to be expressed in the lower genital tract.3) Tumor necrosis factor alpha soluble receptors are increased in the amniotic fluid of women in preterm labor but not in those with normal labor at term. These data suggest that premature labor is not simply labor occurring before fetal maturity (term), but rather a pathologic condition with distinct pathophysiology.4) Evidence that the novel chemokine, RANTES, participates in the host response to intrauterine infection and parturition.